DESCRIPTION: P. gingivalis, a gram-negative anaerobe is an important component of the oral microbiota. Under certain circumstances P. gingivalis can contribute to the initiation and progression of severe and chronic forms of periodontal disease. However, P. gingivalis can also inhabit the oral cavity in the absence of overt disease and can engage in a balanced interaction with host cells. Epithelial cells that line the gingival crevice function both as a physical barrier and as sensors of microbial colonization. The outcome of the interaction between P. gingivalis and gingival epithelial cells, therefore, makes a significant contribution to the degree of equilibrium between host and microbe, and to overall gingival health status. P. gingivalis can manipulate epithelial cell signal transduction pathways in order to direct its entry into the host cell. Internalized P. gingivalis remain viable and accumulate in the perinuclear area; and the epithelial cells do not undergo apoptotic or necrotic cell death. However, gene transcriptional activity is modulated in both host and microbial cells. The goal of this proposal is to provide a greater degree of molecular definition to the mechanisms by which P. gingivalis and gingival epithelial cells interact and adapt to each other. By constructing specific gene knockouts, the functionality of the genes and proteins differentially regulated by P. gingivalis during its association with epithelial cells will be determined. In addition, the means by which P. gingivalis impinges upon epithelial cell apoptotic pathways will be investigated. Finally, the transcriptional profile of epithelial cells that are infected with P. gingivalis will be studied with microarrays. This system-wide approach will provide novel insights into the eukaryotic cellular physiology that accompanies recognition of P. gingivalis and accommodation of intracellular organisms. The ultimate goal of these studies is to use the knowledge gained to develop strategies that could be utilized to intervene in the P. gingivalis epithelial cell interaction to ensure that the outcome is non-harmful to the host.